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Acute p38 MAPK activation decreases force development in ventricular myocytes
Yi Chen1, Ravi Rajashree, Qinghang Liu
1Department of Physiology, University of Tennessee Health Sciences Center, 894 Union Ave., Memphis, TN 38163, USA.
Summary
Arsenite exposure impacts heart muscle function through p38 mitogen-activated protein kinase (MAPK) and other pathways. This study reveals p38 MAPK-dependent and independent mechanisms affecting cardiac contractility and enzyme activity.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- p38 mitogen-activated protein kinase (MAPK) activation is implicated in acute cardiac function.
- Understanding the precise mechanisms of p38 MAPK in cardiac regulation is crucial.
Purpose of the Study:
- To investigate the mechanisms by which p38 MAPK activation influences cardiac function.
- To characterize the role of arsenite in modulating cardiac cellular processes.
Main Methods:
- Adult rat ventricular myocytes were treated with arsenite.
- p38 MAPK phosphorylation was measured and inhibited using SB-203580.
- Protein phosphatase 2a (PP2a) activation, myosin light chain 2 (LC2) phosphorylation, and heat shock protein translocation were assessed.
- Isometric tension and myofibrillar actomyosin Mg2+-ATPase activity were measured in isolated cardiomyocytes.
Main Results:
- Arsenite significantly increased p38 MAPK phosphorylation in a manner sensitive to SB-203580.
- Arsenite induced p38 MAPK-independent PP2a activation and decreased LC2 phosphorylation.
- Arsenite reduced isometric tension via p38 MAPK and lowered Mg2+-ATPase activity independently of p38 MAPK.
- p38 MAPK activation led to heat shock protein 27 translocation to myofilaments.
Conclusions:
- Arsenite affects cardiac function through both p38 MAPK-dependent and independent pathways.
- p38 MAPK-independent changes in PP2a and LC2 contribute to decreased ATPase activity.
- p38 MAPK-dependent myofilament modification leads to reduced myocardial force development.